Rahman M, Lördal M, al-Saffar A, Hellström P M
Department of Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Acta Physiol Scand. 1994 Aug;151(4):497-505. doi: 10.1111/j.1748-1716.1994.tb09772.x.
We have studied the effect of a novel tachykinin, neuropeptide gamma (NP gamma) on small intestinal motility in the rat. Experiments were done in vitro on longitudinal muscle strips of duodenum, and in vivo on the migrating myoelectric complex (MMC) of the small intestine. In vitro, contractile effects of NP gamma were compared with those of a selective neurokinin 1 (NK1) receptor agonist, substance P methyl ester (SPME), and a selective neurokinin 2 (NK2) receptor agonist, Nle10-NKA(4-10)(NleNKA). NP gamma, SPME and NleNKA caused concentration-dependent contractions (P < 0.001). NP gamma was eight-fold more potent than NleNKA, and 118-fold more potent than SPME. Contractile responses to NP gamma were reduced by hexamethonium (P < 0.01) and atropine (P < 0.05). The non-selective NK receptor antagonist spantide I only slightly reduced the contractile response to NP gamma, as did the selective NK1 antagonist GR 82,334, and the selective NK2 antagonist L-659,877 and MEN 10,376. In vivo, effects of NP gamma on the MMC were compared with those of the natural tachykinins substance P (SP) and neurokinin A (NKA). NP gamma disrupted the MMC and induced irregular spiking in a dose-dependent manner from 25 to 100 pmol kg-1 min-1 i.v. (P < 0.05). The effect of NP gamma was more prominent than that of NKA at equal doses, while SP had no effect. Our findings show that NP gamma exerts potent stimulatory effects on small intestinal motility, most likely mediated directly via distinct NK receptors on smooth muscle cells, but also indirectly via a cholinergic link.
我们研究了一种新型速激肽——神经肽γ（NPγ）对大鼠小肠运动的影响。实验分别在体外对十二指肠纵肌条进行，以及在体内对小肠的移行性肌电复合波（MMC）进行。在体外，将NPγ的收缩作用与选择性神经激肽1（NK1）受体激动剂P物质甲酯（SPME）以及选择性神经激肽2（NK2）受体激动剂Nle10-NKA(4-10)（NleNKA）的收缩作用进行比较。NPγ、SPME和NleNKA均引起浓度依赖性收缩（P<0.001）。NPγ的效力比NleNKA高8倍，比SPME高118倍。六甲铵（P<0.01）和阿托品（P<0.05）可降低对NPγ的收缩反应。非选择性NK受体拮抗剂spantide I仅轻微降低对NPγ的收缩反应，选择性NK1拮抗剂GR 82,334、选择性NK2拮抗剂L-659,877和MEN 10,376的作用同样如此。在体内，将NPγ对MMC的作用与天然速激肽P物质（SP）和神经激肽A（NKA）的作用进行比较。NPγ以25至100 pmol kg-1 min-1静脉注射的剂量依赖性方式破坏MMC并诱导不规则尖峰（P<0.05）。在等剂量时，NPγ的作用比NKA更显著，而SP则无作用。我们的研究结果表明，NPγ对小肠运动具有强大的刺激作用，最有可能直接通过平滑肌细胞上不同的NK受体介导，但也可能通过胆碱能联系间接介导。
